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Antibodies to neutralising epitopes synergistically block the interaction of the receptor-binding domain of SARS-CoV-2 to ACE 2. | LitMetric

AI Article Synopsis

  • - The study aims to develop a COVID-19 vaccine that effectively induces antibodies to block the interaction between the Spike protein's receptor-binding domain (RBD) and ACE2, while minimizing the risk of harmful immune responses.
  • - Researchers tested various overlapping peptide sequences from the RBD to identify specific epitopes recognized by antibodies from recovered COVID-19 patients, subsequently using these epitopes to vaccinate mice.
  • - Results showed that certain identified epitopes could induce antibodies that bind the RBD and inhibit its interaction with ACE2, with the strongest effects seen when combining sera from different epitopes, which is crucial for creating effective vaccines against multiple virus strains.

Article Abstract

Objectives: A major COVID-19 vaccine strategy is to induce antibodies that prevent interaction between the Spike protein's receptor-binding domain (RBD) and angiotensin-converting enzyme 2 (ACE2). These vaccines will also induce T-cell responses. However, concerns were raised that aberrant vaccine-induced immune responses may exacerbate disease. We aimed to identify minimal epitopes on the RBD that would induce antibody responses that block the interaction of the RBD and ACE2 as a strategy leading to an effective vaccine with reduced risk of inducing immunopathology.

Methods: We procured a series of overlapping 20-amino acid peptides spanning the RBD and asked which were recognised by plasma from COVID-19 convalescent patients. Identified epitopes were conjugated to diphtheria-toxoid and used to vaccinate mice. Immune sera were tested for binding to the RBD and for their ability to block the interaction of the RBD and ACE2.

Results: Seven putative vaccine epitopes were identified. Memory B-cells (MBCs) specific for one of the epitopes were identified in the blood of convalescent patients. When used to vaccinate mice, six induced antibodies that bound recRBD and three induced antibodies that could partially block the interaction of the RBD and ACE2. However, when the sera were combined in pairs, we observed significantly enhanced inhibition of binding of RBD to ACE2. Two of the peptides were located in the main regions of the RBD known to contact ACE2. Of significant importance to vaccine development, two of the peptides were in regions that are invariant in the UK and South African strains.

Conclusion: COVID-19 convalescent patients have SARS-CoV-2-specific antibodies and MBCs, the specificities of which can be defined with short peptides. Epitope-specific antibodies synergistically block RBD-ACE2 interaction.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937407PMC
http://dx.doi.org/10.1002/cti2.1260DOI Listing

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